Innovation in Flight: Research of the NASA Langley Research Center on Revolutionary Advanced Concepts for Aeronautics

The goal of this publication is to provide an overview of the topic of revolutionary research in aeronautics at Langley, including many examples of research efforts that offer significant potential benefits, but have not yet been applied. The discussion also includes an overview of how innovation and creativity is stimulated within the Center, and a perspective on the future of innovation. The documentation of this topic, especially the scope and experiences of the example research activities covered, is intended to provide background information for future researchers

Exercise intervention and sexual function in advanced prostate cancer: A randomised controlled trial

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: Treatments for prostate cancer such as androgen deprivation therapy (ADT), surgery and radiation therapy can adversely affect sexual, urinary and bowel function. Preliminary research has demonstrated the efficacy of exercise to preserve sexual function in men with localised prostate cancer receiving ADT, though this has yet to be investigated in a metastatic setting. We examined the effects of a 12-week exercise programme comprising resistance, aerobic and flexibility training on sexual health and function in men with advanced prostate cancer. Methods: Patients with prostate cancer (70.0±8.4 year; body mass index 28.7±4.0 kg/m2) with bone metastases (rib/thoracic spine, 66.7%; lumbar spine, 43.9%; pelvis, 75.4%; femur, 40.4%; humerus, 24.6%; other sites, 70.2%) were randomly assigned to supervised exercise 3 days/week (n=28) or usual care (n=29). Sexual health and function were assessed using the International Index of Erectile Function, the Expanded Prostate Cancer Index Composite and the EORTC-PR25 at baseline and 12 weeks. Results: Patients attended 89% of planned sessions and there were no adverse events. After adjusting for baseline values, there was no significant difference between groups for any measure of sexual function and activity (p \u3e 0.05). Additionally, there was no significant difference between groups for urinary and bowel function assessed by the EORTC-PR25 (p \u3e 0.05). Conclusions: A short-Term programme of supervised exercise does not appear to enhance indices of sexual health and function in men with advanced prostate cancer. Limitations of the intervention included the conservative modular exercise programme, which deliberately avoided loading bone metastatic sites

Timing of exercise for muscle strength and physical function in men initiating ADT for prostate cancer

© 2020, The Author(s). Background: Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) results in adverse effects, including reduced muscle strength and physical function, potentially compromising daily functioning. We examined whether it was more efficacious to commence exercise at the onset of ADT rather than later in treatment to counter declines in strength and physical function. Methods: One-hundred-and-four men with PCa (68.3 ± 7.0 years) initiating ADT were randomised to immediate exercise (IMX, n = 54) or delayed exercise (DEL, n = 50) for 12 months. IMX comprised 6 months of supervised resistance/aerobic/impact exercise initiated at the onset of ADT with a 6-month follow-up. DEL comprised 6 months of usual care followed by 6 months of resistance/aerobic/impact exercise. Upper and lower body muscle strength and physical function were assessed at baseline, 6 and 12 months. Results: There was a significant difference for all strength measures at 6 months favouring IMX (P \u3c 0.001), with net differences in leg press, seated row and chest press strength of 19.9 kg (95% CI, 12.3–27.5 kg), 5.6 kg (3.8–7.4 kg) and 4.3 kg (2.7–5.8 kg), respectively. From 7 to 12 months, DEL increased in all strength measures (P \u3c 0.001), with no differences between groups at 12 months. Similarly, physical function improved (P \u3c 0.001) in IMX compared with DEL at 6 months for the 6-m fast walk (−0.2, 95% CI −0.3 to −0.1 s), 400-m walk (−9.7, −14.8 to −4.6 s), stair climb (−0.4, −0.6 to −0.2 s) and chair rise (−1.0, −1.4 to −0.7 s), with no differences between groups by 12 months, except for the 6-m fast walk (P \u3c 0.001). Conclusion: Exercise either at the onset or after 6 months of ADT preserves/enhances muscle strength and physical function. However, to avoid initial treatment-related adverse effects on strength and function, exercise therapy should be implemented with initiation of ADT

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer

Objectives To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. Patients and Methods In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Results Time on ADT significantly moderated the exercise effects on chair rise (βinteraction = −1.3 s, 95% confidence interval [CI] −2.6 to 0.0), whole-body lean mass (βinteraction = 1194 g, 95% CI 234 to 2153) and ASM mass (βinteraction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (βinteraction = −1107 g, 95% CI −2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time −1.5 s (95% CI −2.5 to −0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass −1377 g (95% CI −2156 to −598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (−2.0 s, 95% CI −3.0 to −1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Conclusions Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects

Musculoskeletal comparison of patients with localised versus metastatic prostate cancer

Abstract of a presentation at the 2nd Prostate Cancer World Congress, Australia, 17-21 August 201

Immediate versus delayed exercise in men initiating androgen deprivation: effects on bone density and soft tissue composition

OBJECTIVES: To examine whether it is more efficacious to commence exercise medicine in men with prostate cancer at the onset of androgen-deprivation therapy (ADT) rather than later on during treatment to preserve bone and soft-tissue composition, as ADT results in adverse effects including: reduced bone mineral density (BMD), loss of muscle mass, and increased fat mass (FM). PATIENTS AND METHODS: In all, 104 patients with prostate cancer, aged 48-84 years initiating ADT, were randomised to immediate exercise (IMEX, n = 54) or delayed exercise (DEL, n = 50) conditions. The former consisted of 6 months of supervised resistance/aerobic/impact exercise and the latter comprised 6 months of usual care followed by 6 months of the identical exercise programme. Regional and whole body BMD, lean mass (LM), whole body FM and trunk FM, and appendicular skeletal muscle (ASM) were assessed by dual X-ray absorptiometry, and muscle density by peripheral quantitative computed tomography at baseline, and at 6 and 12 months. RESULTS: There was a significant time effect (P \u3c 0.001) for whole body, spine and hip BMD with a progressive loss in the IMEX and DEL groups, although lumbar spine BMD was largely preserved in the IMEX group at 6 months compared with the DEL group (-0.4% vs -1.6%). LM, ASM, and muscle density were preserved in the IMEX group at 6 months, declined in the DEL group at 6 months (-1.4% to -2.5%) and then recovered at 12 months after training. FM and trunk FM increased (P \u3c 0.001) over the 12-month period in the IMEX (7.8% and 4.5%, respectively) and DEL groups (6.5% and 4.3%, respectively). CONCLUSIONS: Commencing exercise at the onset of ADT preserves lumbar spine BMD, muscle mass, and muscle density. To avoid treatment-related adverse musculoskeletal effects, exercise medicine should be prescribed and commenced at the onset of ADT

Branding and a child’s brain: an fMRI study of neural responses to logos

Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children’s brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing

Dopamine transporter genotype is associated with a lateralized resistance to distraction during attention selection

Although lateral asymmetries in orienting behavior are evident across species and have been linked to interhemispheric asymmetries in dopamine signaling, the relative contribution of attentional versus motoric processes remains unclear. Here we took a cognitive genetic approach to adjudicate between roles for dopamine in attentional versus response selection. A sample of nonclinical adult humans (N = 518) performed three cognitive tasks (spatial attentional competition, spatial cueing, and flanker tasks) that varied in the degree to which they required participants to resolve attentional or response competition. All participants were genotyped for two putatively functional tandem repeat polymorphisms of the dopamine transporter gene (DAT1; SLC6A3), which are argued to influence the level of available synaptic dopamine and confer risk to disorders of inattention. DAT1 genotype modulated the task-specific effects of the various task-irrelevant stimuli across both the spatial competition and spatial cueing but not flanker tasks. Specifically, compared with individuals carrying one or two copies of the 10-repeat DAT1 allele, individuals without this allele demonstrated an immunity to distraction, such that response times were unaffected by increases in the number of distractor stimuli, particularly when these were presented predominantly in the left hemifield. All three genotype groups exhibited uniform costs of resolving leftward response selection in a standard flanker task. None of these significant effects could be explained by speed–accuracy trade-offs, suggesting that participants without the 10-repeat allele of the DAT1 tandem repeat polymorphism possess an enhanced attentional ability to suppress task-irrelevant stimuli in the left hemifield

Influence of individuals’ determinants including vaccine type on cellular and humoral responses to SARS-CoV-2 vaccination

Vaccine development targeting SARS-CoV-2 in 2020 was of critical importance in reducing COVID-19 severity and mortality. In the U.K. during the initial roll-out most individuals either received two doses of Pfizer COVID-19 vaccine (BNT162b2) or the adenovirus-based vaccine from Oxford/AstraZeneca (ChAdOx1-nCoV-19). There are conflicting data as to the impact of age, sex and body habitus on cellular and humoral responses to vaccination, and most studies in this area have focused on determinants of mRNA vaccine immunogenicity. Here, we studied a cohort of participants in a population-based longitudinal study (COVIDENCE UK) to determine the influence of age, sex, body mass index (BMI) and pre-vaccination anti-Spike (anti-S) antibody status on vaccine-induced humoral and cellular immune responses to two doses of BNT162b2 or ChAdOx-n-CoV-19 vaccination. Younger age and pre-vaccination anti-S seropositivity were both associated with stronger antibody responses to vaccination. BNT162b2 generated higher neutralising and anti-S antibody titres to vaccination than ChAdOx1-nCoV-19, but cellular responses to the two vaccines were no different. Irrespective of vaccine type, increasing age was also associated with decreased frequency of cytokine double-positive CD4+T cells. Increasing BMI was associated with reduced frequency of SARS-CoV-2-specific TNF+CD8% T cells for both vaccines. Together, our findings demonstrate that increasing age and BMI are associated with attenuated cellular and humoral responses to SARS-CoV-2 vaccination. Whilst both vaccines induced T cell responses, BNT162b2 induced significantly elevated humoral immune response as compared to ChAdOx-n-CoV-19

Weight loss for overweight and obese patients with prostate cancer: A study protocol of a randomised trial comparing clinic-based versus telehealth delivered exercise and nutrition intervention (the TelEX trial)

Introduction Obese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer. Methods and analysis A single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥ 25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7-12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches. Ethics and dissemination Ethics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021-02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings. Trial registration number: ACTRN12621001312831